Generating solutions

Cancer is the most common cause of non-accidental death in children from infancy to young adulthood. In Canada, ~1,400 children (0-18 years of age) will be diagnosed with cancer every year. Approximately 200 will die and many more will live with life-long complications of their disease and treatments. Thus, cancer and cancer-related illness remains an unacceptable social and economic burden for Canada and Canadian families.

Although overall survival for children with cancer has improved substantially over the last three decades, significant challenges remain. A considerable proportion of childhood cancers remain incurable, or can only be cured with treatments that leave a child with life-long mental or physical disabilities. Furthermore, for children with tumours that recur or that spread to other parts of the body, current therapies are largely unsuccessful. To further improve survival, the quality of life of children surviving their cancer, and alleviate the socio-economic burden on their families, it is important to understand why specific types of tumours spread or come back, and why some of the most aggressive tumours are so resistant to therapy.

To this end, a group of highly accomplished Canadian researchers and clinicians, who are experts in childhood cancer and novel DNA sequencing technologies, have joined forces to use one of the most powerful gene sequencing technologies ever developed, to probe the genomes (DNA) of four of the most challenging childhood cancers known. The ultimate aim of this comprehensive project is to use the newly discovered genetic information about these cancers that we uncover, to gain insight into targets and new therapies that may be developed for these devastating diseases.

The researchers will use this powerful, leading edge “next generation sequencing” technology to rapidly scan the DNA of the entire human genome that is contained in tumour cells. They will examine and directly compare the genetic signature of primary tumour cells and tumour cells that have spread (metastasized) or relapsed in childhood medulloblastoma (brain cancer), metastatic osteosarcoma (bone cancer) and recurrent leukemia (cancer of white blood cells), to uncover genetic abnormalities that direct tumour cells to spread or become resistant to treatment. In addition, they will determine the gene signatures of three highly lethal childhood brain tumours to uncover new genes that may be targets for new drug therapies. Our studies will generate an unprecedented view of the tumour genomes in these diseases. This will not only provide short-term potential for improving tailored therapies for children with these lethal cancers, but in the longer term will enable the development of new drugs for patients who otherwise have limited options for treatment.

This project also provides the opportunity to study the many ethical issues that arise in deciding when and how best to provide the results from genetic studies on childhood cancers back to the patients and their families. In the short-term, this multi-disciplinary, cross-Canada national study will redefine the genetic basis of aggressive childhood cancers, which we expect will lead to a better understanding of the potential role for novel ‘targeted’ therapies for this group of diseases. In the longer term, the results will lead to improved survival and reduced long-term consequences for children with cancer.